Researchers at the Dana-Farber Cancer Institute have found that in mice, implanting a small disc of gel during surgery that slowly releases an immune-boosting drug afterward appears to help keep the cancer from recurring.
The researchers tested more than a hundred mice with breast cancer, lung cancer or melanoma. After their tumors were removed, the researchers implanted a dime-sized gel disc that releases an immune-boosting drug for days to weeks afterward.
The study’s senior author, Dr. Michael Goldberg, explains what he, lead author Chun Gwon Park, and colleagues found: a technique that may hold promise for human cancer patients as well, to improve their odds after a tumor is surgically removed. The drug emitted by the gel boosts the patient’s own immune system so that it can fight any residual cancer. Our exchange, edited:
How would you sum up what you did?
Cancer immunotherapy can confer durable survival benefit, but the percentage of patients who respond to this approach remains modest. We optimized the formulation of a biodegradable hydrogel that can concentrate drugs that boost immune cells at a site of interest and release these drugs over an extended period of time.
We then placed the hydrogels into the empty space left behind after surgically resecting tumors from mice, enabling the hydrogels to release immune-stimulating drugs into an environment that is otherwise associated with immune suppression and wound healing.
Such prolonged localized release can reduce systemic toxicity and was shown to cure a much higher percentage of animals than administration of the same therapy in solution, whether systemically or locally.
The ability to control the timing and location of drug delivery may be rather useful for applications at the intersection of surgery and immunotherapy.
And how would you sum up the beneficial effect you measured? (in particular, what was the size of the effect in terms of mice remaining resistant to cancer?)
For mice harboring breast cancer, we observed durable survival benefit among 65 percent of treated mice (of which more than 100 were evaluated in this study).
For comparison, among mice that received surgery alone, we observed durable survival benefit among only 10 percent of mice.
We confirmed that mice were functionally cured by re-challenging a portion of them with fresh cancer cells, and 100 percent of the mice that had benefited from the hydrogel rejected the second tumor, indicating that their immune systems had generated a memory response against the cancer.
In contrast, 100 percent of mice that did not receive the hydrogel succumbed to such a challenge within 50 days.
In additional studies, we observed similar durable survival benefit among mice harboring lung cancer or melanoma, though we have assessed far fewer mice with these cancer types to date.
Can you give a sense of how soon this may be tested in human patients? And how would you describe what this might mean for them?
I would be remiss to provide a specific timeline for clinical translation, but we are very hopeful that this technology will be tested in patients in the not-too-distant future.
We are speaking with oncologists who specialize across various cancer types to guide the translational strategy. Their insights should help us to select initial indications for this intervention.
In terms of what this might mean for human cancer patients, we envision surgeons placing biodegradable hydrogels loaded with immunotherapy into the resection site following tumor removal with the goal of preventing local tumor recurrence, as well as eliminating distal metastases, thereby dramatically improving the long-term survival of cancer patients.
There has long been talk that surgery can sometimes spur metastasis — is that now considered correct? And could this localized immunotherapy be the answer to it?
I think that a good number of scientists and clinicians would agree with the notion that surgery can influence cancer recurrence and spread, though it’s not entirely clear whether surgery directly spurs metastasis by unintentionally spreading cancer cells during the actual surgical procedure or generates a physiological response that promotes the outgrowth of existing micrometastases that were not removed by the surgery.
I think that it would be more appropriate to suggest that localized immunotherapy may be “an answer” rather than “the answer,” as several approaches merit consideration for evaluation in patients.
Our preclinical data indicate that extended localized release of immunotherapy in the tumor resection site works well in multiple mouse models of spontaneously metastasizing solid tumors, but only clinical data will answer whether localized immunotherapy can truly prevent metastasis and/or potentially eliminate existing metastases in humans.
Very roughly, how much might these gel discs cost if they were used in humans?
I imagine that a company could answer this question much better than I can, though I can confirm that the materials that we have used to generate the discs are natural and FDA-approved. For example, hyaluronan — which is naturally found in many joints — is approved for injection into the knee for treatment of osteoarthritis.
Do you expect that they may become a routine element of cancer surgery?
That is certainly my hope. This approach permits localized delivery to internal organs of drugs that are very potent but are currently limited to accessible tumors, as they must be injected directly into lesions; challengingly, most cancer patients do not have tumors that are readily accessible for injection.
If the data in patients are consistent with what we have observed in mice, then one might expect that this intervention could indeed become a routine element of cancer surgery. I would be delighted if this were to come to pass.
